The tumour-associated carbonic anhydrases CA II, CA IX and CA XII in a group of medulloblastomas and supratentorial primitive neuroectodermal tumours: an association of CA IX with poor prognosis

Abstract

Background: Medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumours (PNETs) are the most common highly aggressive paediatric brain tumours. In spite of extensive research on these tumours, there are only few known biomarkers or therapeutic target proteins, and the prognosis of patients with these tumours remains poor. Our aim was to investigate whether carbonic anhydrases (CAs), enzymes commonly overexpressed in various tumours including glioblastomas and oligodendrogliomas, are present in MBs and PNETs, and whether their expression can be correlated with patient prognosis.

Methods: We determined the expression of the tumour-associated carbonic anhydrases CA II, CA IX and CA XII in a series of MB/PNET specimens (n = 39) using immunohistochemistry.

Results: Endothelial CA II, cytoplasmic CA II, CA IX and CA XII were expressed in 49%, 73%, 23% and 11% of the tumours, respectively. CA II was detected in the neovessel endothelium and the tumour cell cytoplasm. CA IX was mainly expressed in the tumour cells located in perinecrotic areas. CA XII showed the most homogenous distribution within the tumours. Importantly, CA IX expression predicted poor prognosis in both univariate (p = 0.041) and multivariate analyses (p = 0.016).

Conclusions: We suggest that CA IX should be considered a potential prognostic and therapeutic target in MBs and PNETs.

Figure 1

Representative immunostaining of CA enzymes in MBs. Panel A shows no immunoreaction for CA IX, whereas the tumour in panel B is strongly positive. Panel C demonstrates CA XII-positive immunoreactivity in tumour cells. In panel D, CA II-positive immunostaining is confined to the endothelium of small blood vessels (arrows). All magnifications ×400.

Figure 2

Kaplan-Meier curves showing overall survival of patients with MB or PNET categorised by: A. tumour cell-associated CA II, B. endothelial CA II, C. CA IX (p = 0.041; log-rank test), and D. CA XII immunostaining results.